The immediate goal of these studies is to develop methods for efficiently introducing human globin genes into hemopoietic cells both in order to study their tissue specific regulation. A hybrid SV40 virus construct, which contains the prokaryotic gene coding for chloramphenicol acetyl transferase (CAT), transiently expressed the CAT gene in hemopoietic cell lines and fresh bone marrow cells of humans and other species into which it had been transferred. We have made use of helper free double recombinant adenoviruses containing the neo gene and human globin genes. These viruses can successfully transfer both genes into K562 and other cell lines. Adenoviral mediated transfer of a Gamma-Beta hybrid globin gene and a Beta globin gene resulted in expression of the Gamma-Beta but not the Beta gene. Neither globin gene is efficiently expressed in fibroblasts demonstrating tissue-specific expression in human cell lines. As adenoviral vectors have not proven useful for gene transfer into stem cells of bone marrow, retroviral vectors containing a human globin gene and a selectable marker gene have been constructed. A Gamma-Beta hybrid globin gene has been efficiently expressed in MEL cells following retroviral mediated gene transfer, showing high levels of normally initiated, spliced, and terminated Gamma-Beta mRNA. Protein expression is also seen. This high titer globin containing retroviral vector is now being used to achieve transfer of globin genes into hemopoietic progenitor and stem cells of mouse, monkey, and man.